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The interaction of photo-responsive surfactants with biological macromolecules

THE INTERACTION OF PHOTO-RESPONSIVE SURFACTANTS WITH BIOLOGICAL MACROMOLECULES
by
Khiza L. Mazwi
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(MATERIALS SCIENCE)
December 2012
Copyright 2012 Khiza L. Mazwi

The interaction of photo-responsive surfactants with proteins has been considered as a means to exert reversible control over a number of aspects of protein structure and function. The azobenzene trimethylammonium bromide (azoTAB) family of cationic surfactants undergo a photo-reversible cis to trans isomerization upon exposure to light of the appropriate wavelength. The trans form of the molecule has a lower dipole moment across its azo linkage, and is more hydrophobic than the cis isomer. This results in a higher binding affinity with proteins for the trans isomer, inducing a greater degree of unfolding of tertiary and secondary structures. The surfactant has been applied to the study of the amyloid fibrillation pathway in insulin, in which the protein self-associates into long, insoluble, rod-like structures. The fibrillation rate in insulin is enhanced in the presence of the trans- isomer while the formation of fibrils is largely inhibited in the presence of the cis- isomer, where amorphous aggregates are observed instead. Additionally early fibrillar species formed in the trans-azoTAB assays exhibit a greater tendency to lateral aggregation than do structures in the pure protein, resulting in a more truncated, bundled final aggregate morphology. Use of the surfactants as a means to control protein quaternary solution structure has also been explored in the subunit dissociation of tetrameric catalase. In the presence of azoTAB surfactants, catalase dissociates first into a super-active dimer, then at higher concentrations into an aggregation prone monomer. Finally, the structural changes associated with azoTAB-induced unfolding of the two domain protein papain are tracked. The denaturation pathway involves a progressive loss in secondary structure with increasing azoTAB concentration, along with a relaxation of the compact tertiary structure, and a spatial separation of the two domains. A number of complementary experimental techniques are combined to determine the solution structure of non-native protein conformations, including light scattering, circular dichroism and small angle neutron scattering.

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THE INTERACTION OF PHOTO-RESPONSIVE SURFACTANTS WITH BIOLOGICAL MACROMOLECULES
by
Khiza L. Mazwi
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(MATERIALS SCIENCE)
December 2012
Copyright 2012 Khiza L. Mazwi